CHAPTER 24 – Evolution of Protein Molecules

Inference of macromolecular assemblies from crystalline state.

On the Nature of Allosteric Transitions: A Plausible Model

Solvent content of protein crystals.

Stanford Moore, William Stein, and Anfinsen were awarded the Nobel Prize in Chemistry in 1972 for \"their contribution\n to the understanding of the connection between chemical structure and catalytic activity of the active center of the ribonuclease\n molecule.\" In his Nobel Lecture, Anfinsen provided a sketch of the rich history of research that provided the foundation\n for his work on protein folding and the \"Thermodynamic Hypothesis,\" and outlined potential avenues of current and\n future scientific exploration.

https://web.iitd.ac.in/~amittal/1973_Anfinsen_Science.pdf

Principles that Govern the Folding of Protein Chains

▪ Abstract In 1970, Perutz tried to put the allosteric mechanism of hemoglobin, proposed by Monod, Wyman and Changeux in 1965, on a stereochemical basis. He interpreted their two-state model in terms of an equilibrium between two alternative structures, a tense one (T) with low oxygen affinity, constrained by salt-bridges between the C-termini of the four subunits, and a relaxed one (R) lacking these bridges. The equilibrium was thought to be governed primarily by the positions of the iron atoms relative to the porphyrin: out-of-plane in five-coordinated, high-spin deoxyhemoglobin, and in-plane in six-coordinated, low-spin oxyhemoglobin. The tension exercised by the salt-bridges in the T-structure was to be transmitted to the heme-linked histidines and to restrain the movement of the iron atoms into the porphyrin plane that is necessary for oxygen binding. At the β-hemes, the distal valine and histidine block the oxygen-combining site in the T-structure; its tension was thought to strengthen that blockage...

The stereochemical mechanism of the cooperative effects in hemoglobin revisited

https://www.cell.com/trends/biochemical-sciences/pdf/S0968-0004(98)01350-4.pdf

Glutamine repeats and neurodegenerative diseases: molecular aspects

Structure and function of haemoglobin

MOST enzymes are quickly inactivated above about 55 °C but those from thermophile bacteria are stable for long periods at higher temperatures1. We do not know why because so far their structures have proved too complex. For example although the tertiary and quaternary structures of the enzyme glyceraldehyde phosphate dehydrogenase from lobster muscle and from Bacterium stearothermophilus are alike their amino acid sequences differ by more than 130 out of some 330 positions which makes it hard to decide why the stearothermophilus enzyme is more stable. The electron transfer protein ferredoxin offers a better chance because its single polypeptide chain contains fewer than 60 residues; its structure is known and its heat stability and amino acid sequence have been determined in both mesophile and thermophile bacteria. We have built an atomic model of this protein, replaced its amino acid side chains in turn to correspond to the published sequences and searched for possible causes of the greater heat stability of ferredoxins from thermophile bacteria. We found that it arises mainly from external salt bridges linking residues near the amino terminus to others near the carboxy terminus. Haemoglobin A2 a minor fraction of adult human haemoglobin which is a little more heat stable than the major fraction, haemoglobin A, seemed another good choice because its amino acid sequence differs from that of A at only 10 positions. The atomic model suggests that at only two of these positions are the replacements likely to contribute to the extra stability of haemoglobin A2 one replacement providing an extra hydrogen bond between the α1 and β1 subunits and the other adding two non-polar interactions to a surface crevice within the β subunits. To account for the increased heat stability of the two proteins the extra bond energy provided by these interactions need not be larger than 10 kJ for ferredoxin or 5 kJ for haemoglobin A2.

Max F. Perutz

Papers

The stereochemical mechanism of the cooperative effects in hemoglobin revisited

Glutamine repeats and neurodegenerative diseases: molecular aspects

Structure and function of haemoglobin

Stereochemical basis of heat stability in bacterial ferredoxins and in haemoglobin A2.

Stereochemistry of cooperative mechanisms in hemoglobin